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Effect of particle size on the cytotoxicity of zinc oxide nanoparticles in rat and human intestinal cell models
Citation:
Henson, T., J. Navratilova, K. Bradham, K. Rogers, AND M. Hughes. Effect of particle size on the cytotoxicity of zinc oxide nanoparticles in rat and human intestinal cell models. Society of Toxicology Annual Meeting, Baltimore, Maryland, March 10 - 14, 2019.
Impact/Purpose:
Human exposure to zinc oxide nanoparticles (ZnO NPs) may occur by the oral route. In this study we examined ZnO NPs cytotoxicity in a rat intestinal cell model and human cell model. The rat cells were more sensitive to the NPs than the human cells with regard to cytotoxicity. Similar results were conducted with ZnSO4, a source of zinc ions. The results suggest that ZnO NPs dissolve to zinc ions, which elicit a cytotoxic response.
Description:
Zinc oxide nanoparticles (NPs) have several commercial applications ranging from catalysts to semiconductors. ZnO NPs are toxic to bacteria, aquatic organisms and human cells. There is a potential for human oral exposure to ZnO NPs following accidental or intentional ingestion, hand-to-mouth activity, or mucociliary transport following inhalation. This study assessed the cytotoxic effects of ZnO NPs (10 and 150 nm) in rat and human intestinal cells. The rat cells are a 2-dimensional model (IEC-6) while the human cells are a 3-dimensional highly differentiated model. Three-dimensional cell cultures offer greater predictability of in vivo toxicity than comparable 2-dimensional cell cultures because of their complexity and their overall functions are more similar to native tissues. The effect of dose (0.1 - 100 μg/mL rat; 1-100 μg/mL, human), time (4 and 24 h) and particle size were evaluated. ZnSO4 (0.1 - 100 μg Zn/mL) was tested for 4 and 24 h to assess Zn ion toxicity. IEC-6 cells were plated at 60K/well in a 96 well plate 24 h before dosing. Media with 10% fetal bovine serum was the negative control. Triton X-100 (0.3%) was the positive control. ZnO NPs were suspended in media and probe sonicated before dosing. Following incubation, the cells were washed with media. Cytotoxicity was assessed using a colorimetric method that measures mitochondrial activity (MTS, rat; MTT, human). In IEC-6 cells, a significant dose-dependent (p<0.0001) decrease in viability was observed after 4- and 24-h incubation of the 10 and 150 nm ZnO NPs. For both particles in IEC-6 cells, at 4 h, viability decreased ~50% at ≥ 50 μg/mL; at 24 h, viability decreased ~75% at ≥ 25 μg/mL. In human cells, decreases in viability were significantly decreased, but no greater than 10% at 4 or 24-h for both ZnO NPs. For ZnSO4, similar results to the ZnO NPs were observed in both tissues at 4 and 24 h. Particle size does not appear to have a role in the cytotoxicity of ZnO NPs in these cells. In addition, the similar cytotoxicity profile of ZnO NPs and Zn2+ ions suggests dissolution of the NPs may have a greater impact than particle size. (This abstract does not represent US EPA policy.)